title: Caveolin-1 interacts with Derlin-1 and promotes ubiquitination and degradation of cyclooxygenase-2 via collaboration with p97 complex.
abstract: Caveolin-1 (Cav-1) interacts with and mediates protein trafficking and various cellular functions. Derlin-1 is a candidate for the retrotranslocation channel of endoplasmic reticulum proteins. However, little is known about how Derlin-1 mediates glycosylated protein degradation. Here, we identified Cav-1 as a key player in Derlin-1- and p97-mediated cyclooxygenase 2 (COX-2) ubiquitination and degradation. Derlin-1 augmented the interaction of Cav-1 and COX-2 and mediated the degradation of COX-2 in a COX-2 C terminus-dependent manner. Suppression of Cav-1 decreased the ubiquitination of COX-2, and mutation of Asn-594 to Ala to disrupt N-glycosylation at the C terminus of COX-2 reduced the interaction of COX-2 with Cav-1 but not Derlin-1. Moreover, suppression of p97 increased the ubiquitination of COX-2 and up-regulated COX-2 but not COX-1. Cav-1 enhanced the interaction of p97 with Ufd1 and Derlin-1 and collaborated with p97 to interact with COX-2. Cav-1 may be a cofactor in the interaction of Derlin-1 and N-glycosylated COX-2 and may facilitate Derlin-1- and p97 complex-mediated COX-2 ubiquitination, retrotranslocation, and degradation.
authors.affiliation: From the Cardiovascular Division, Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Shu-Fen
authors.initials: SF
authors.lastname: Chen
authors.forename: Chun-Hu
authors.initials: CH
authors.lastname: Wu
authors.forename: Yen-Ming
authors.initials: YM
authors.lastname: Lee
authors.forename: Kabik
authors.initials: K
authors.lastname: Tam
authors.forename: Yi-Chen
authors.initials: YC
authors.lastname: Tsai
authors.forename: Jun-Yang
authors.initials: JY
authors.lastname: Liou
authors.forename: Song-Kun
authors.initials: SK
authors.lastname: Shyue
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D059748:Proteolysis; D054875:Ubiquitination / Q000502:physiology*; D000074405:Valosin Containing Protein
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; C495540:CAV1 protein, human; C495541:Cav1 protein, mouse; D051242:Caveolin 1; D018797:Cell Cycle Proteins; C487709:DERL1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D011506:Proteins; C491497:UFD1 protein, human; C107396:Ufd1 protein, mouse; C530424:derlin-1 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D000251:Adenosine Triphosphatases; D000074405:Valosin Containing Protein
keywords: Caveolin; Caveolin-1; Cyclooxygenase (COX) Pathway; Cyclooxygenase-2; Derlin-1; ER-associated Degradation; Protein Degradation; Ubiquitination; p97